Mason-Pfizer monkey virus, the prototypic type-D retrovirus, provides a unique system for studying retroviral replication in that the processes of capsid assembly, intracellular transport, and budding/release are spatially and temporally separated. This is in contrast to the C-type morphogenesis of most other retroviruses, where the processes of assembly, budding, and virus release all take place at the plasma membrane. Although the functional domains of the Gag polyprotein precursor have been found to play important roles in Gag polymerization, intracellular targeting and transport, and membrane extension and virus release, many of these events are also likely to involve host cell components. The major goal of this proposal is to identify and define the role of host cell proteins in viral assembly and transport. We plan to utilize a combination of approaches, including antibody co-precipitation, yeast two-hybrid systems, and gene chip technology to identify and characterize novel host cell components and cellular chaperone proteins involved in the M-PMV capsid assembly/transport process. These approaches will extend our understanding of the molecular events involved in retrovirus assembly and will pave the way for rational approaches to develop therapeutics that can interfere with these key events in the virus life cycle.